Hydrochloric Acid → 1-[4-(Methoxymethyl)phenyl]-1-(4-methoxyphenyl)methanamine

HRID 2059739Notes

Reaction equation

HRID 2059739 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([Mg]Br)=[CH:16][CH:15]=1.[BH4-].[Na+].Cl>C1COCC1>[CH3:1][O:2][CH2:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]([C:17]2[CH:18]=[CH:19][C:14]([O:13][CH3:12])=[CH:15][CH:16]=2)[NH2:9])=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 132851414-(Methoxymethyl)benzonitrileHCID 178491912HCID 178491912, compound

Product 1

HCID 578784351-[4-(Methoxymethyl)phenyl]-1-(4-methoxyphenyl)methanamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the product of Step A (1.5 g, 10.19 mmol) in THF (15 mL) was added 4-methoxyphenylmagnesium bromide (11.21 mL, 11.21 mmol, 1.0 M). The reaction aged at rt for 3.5 h and was concentrated. The residue was dissolved in MeOH (20 mL) and then slowly treated with NaBH4 (0.386 g, 10.19 mmol). The reaction was stirred at rt overnight, concentrated and treated with aq. HCl (15 mL, 30 mmol, 2.0 M). The aqueous portion was extracted with EtOAc (2×) and the combined organic layers were washed with a 1:1 solution of aq. 2.0 M NaOH/brine, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel gradient eluted with 0-100% EtOAc/hexane to afford the title compound. HPLC/MS: 241.0 (M—NH2)+; Rt=1.91 min.

Workup

  1. concentrationwas concentrated
  2. dissolutionThe residue was dissolved in MeOH (20 mL)
  3. concentrationconcentrated
  4. extractionThe aqueous portion was extracted with EtOAc (2×)
  5. washthe combined organic layers were washed with a 1:1 solution of aq. 2.0 M NaOH/brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography on silica gel gradient
  10. washeluted with 0-100% EtOAc/hexane

Sources & evidence

ORD record
ord-567b65bee85b4e419bb074de8ec161ab
Source dataset
uspto-grants-2012_10
Patent number
US08278304B2

Reaction notes

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